The present invention relates to a method for promoting the healing of bone tissue which is subjected to surgery or other interventional procedures. The invention also relates to associated apparatus for use in the method.
Boyer described the use of electrical energy to heal tibial fractures in 1816 (Boyer, 1816). Wolff published in 1892 what is know today as Wolff's Law, stating the structure of bone adapts to changes in its stressed environment (Behrens, 2013). Thus the application of energy to bone creates the potential for artificial stresses that can result in the bone responding. The response is the stimulatory result of the application of artificial stresses.
The application of artificial stresses to bone by energy is bounded or delimited by other potential tissue effects. The most prevalent of these is the production of heat. Continuous application of energy to bone can result in thermal damage to either the application site or the treatment site. Thus upper limit of application of energy that can result in therapeutic bone stimulation is the point at which the application of that energy causes thermal damage.
This upper limit was a prohibiting factor in the use of ultrasound as an energy source for application to bone in general. A variety of treatment modalities for therapeutic application of ultrasound were explored with success from the 1930's forward, but bone treatment was viewed as a limitation due to the potential to damage the bone rather than stimulate it.
In 1950, Maintz published the first study describing the positive stimulatory effect of ultrasound on bone (Schortinghuis, 2003). The study in rabbits did not confirm an accelerated bone healing effect by ultrasound, but noted that periosteal new bone formation could be produced. The first human study reporting the treatment of slow or non-uniting fractures by ultrasound was published in 1953 (H Hippe, 1953).
A renewed interest in the use of ultrasound for bone stimulation and healing began with research using low dose pulsed ultrasound to overcome the issue of thermal damage (Shiro, 1964). This type of application of energy employed pulsed ultrasound at an intensity of 0.2 W/cm2. The low energy density application stays below a threshold of thermal build up avoiding the potential for thermal damage. The challenge with lower dose energy applications is to be above the lower limit threshold of clinical effect. So the application of energy must be of sufficient density and duration to cause an effect to occur without causing thermal damage at the treatment site.
Low intensity pulsed ultrasound allows for application of the energy from a distant site, resulting in a non-invasive treatment. The application of the energy is easily transmitted from a non-invasive site to the internal targeted bone that requires stimulation or healing. Ultrasound waves transmit well through tissue, making a potential treatment application one that starts at the skin and continues to the treatment site and beyond. This non-invasive approach requires energy levels at the skin to be higher to compensate for the required energy densities that will be between the lower limit of tissue (bone) response and the upper limit of thermal damage.
Electrical energy can be transmitted from the skin to the targeted area. The challenge in utilizing electrical energy for non-invasive applications is the potential for both muscle and nerve tissue in the transmitting path to cause either contractions or pain. The type of tissue in the transmission path and the potential for unwanted tissue response not at the targeted area represents another limitation to the application of energy for bone stimulation or healing.
One method to overcome several of these limitations is the implantation of devices that remain resident in the body. The implantation results in a closer proximity to the treatment site, reducing the risk for unwanted tissue response in the transmission path. Additionally in the implantation approach the risk is reduced for thermal damage at the skin, in the transmission path, or at the targeted treatment zone because lower energy densities are required due to the closer proximity of the energy source to the targeted treatment zone. For example, implantable devices can include DC stimulation devices or pulsed electromagnetic fields (PEMF) which implant the applicators at the fusion site and the power source is either implanted or delivered by inductive coupling (Gan, 2006). The limitation of this approach is the need to implant a device in the patient for a significant period of time postoperatively in order to achieve the treatment effect.
The challenge in either a non-invasive only or implantable device only is to remain with the lower and upper limits of energy density to enable effective bone stimulation and healing. Both approaches mitigate the problem of energy density deposition remaining within the upper and lower threshold limits by applying energy over a long duration and frequency. For example, low intensity pulsed ultrasound (LIPUS) treatment protocols may range, with 20 minute daily application, from 2 weeks to 40 days (Erdogan, 2009). The limitation of long duration or frequency of treatment application is the reliance on the patient for compliance in consistent application.
A variety of methods have been described to stimulate bone in order to encourage healing. For example, U.S. Pat. No. 4,530,360 Duarte describes a method of applying pulses of ultrasound non-invasively daily over a period of weeks to months. The power density is noted to be below thermal damage thresholds of the application and target treatment sites. The limitation in this approach is the need to apply sufficient amounts of power density to transmit from the skin to the bone treatment site, while staying below the thermal damage threshold. The resulting treatment parameters require a long duration of application measured in weeks to months.
U.S. Pat. No. 5,191,880 describes a method to mechanically stimulate bone growth or healing. The application of either mechanical, electrical or ultrasound energy at high frequencies (between 10 to 50 hertz) mimics the resonant frequency that naturally occurs in movements such as walking, to produce mechanical loads on the bone. These mechanical loads are meant to stress the bone in order to promote a growth or healing response. The limitation to this approach is that the stress imparted to the bone is inherently damaging. The underlying condition for lack of bone density (osteopenia for example) would limit the response to the applied mechanical stresses. This method does not attempt to stimulate bone cells directly to initiate bone cellular activation and upregulation of genes and growth factors.
U.S. Pat. No. 5,441,527 describes a method for an implantable bone stimulation device that delivers alternating current. The energy is delivered over a period of time and the implant is left in place during the entire treatment regimen. The inherent limitation of this device is the need to leave behind an implantable device in order to derive the benefit of delivering therapeutic bone stimulation at or near the target.
U.S. Pat. No. 5,496,256 describes an implant with disposable ultrasound transducers for healing in dental applications. The implant involves the application of ultrasound energy to accelerate healing of bone grafts in the jaw. The limitation of this approach is the use of an ultrasonic implant held in place by an implantable screw in order to aid healing of either another implant or a bone graft.
U.S. Pat. No. 5,547,459 describes a non-invasive ultrasound bone stimulation device that utilizes a set of ultrasonic signals to determine the optimal dose of exogenous application. The resulting dose is delivered with a spatial-average time-average (SATA) power density of around 45 mW/cm2. The limitation of this device is the need to deliver a higher power density at the exogenous application site in order to achieve the optimal dose at the bone treatment site.
While a number of non-invasive or implantable bone stimulation devices have been previously disclosed, what does not exist and what would be beneficial to the market is a method to apply bone stimulation directly during interventional procedures, and or in combination with postoperative and/or pre operative bone stimulation applications to assist bone healing post intervention.